Recently, when preparations such as plasma fraction preparations and bio-medicines are administered to human bodies, there is a sense of growing crisis regarding pathogens such as bacteria, viruses and pathogenic proteins which might be contained in the preparations, and a membrane filtration method using separating membranes is increasingly noticed as a useful means for physical removal of these pathogens. Microporous membranes used for these purposes are generally called medical separating membranes.
Viruses include microviruses such as parvoviruses of 18-24 nm in diameter, polioviruses of 25-30 nm in diameter, EMC viruses of 28-30 nm in diameter, and type A hepatitis viruses of 28-30 nm in diameter. Microporous membranes of about 50 nm in pore diameter can be utilized as pre-filters for this microvirus group.
Viruses having medium sizes include type B hepatitis viruses of 40-45 nm in diameter, SV40 viruses of 45-55 nm in diameter, BVD viruses of 40-60 nm in diameter, sindbis viruses of 60-70 nm in diameter, etc., and viruses having larger sizes include HIV viruses of 80-100 nm in diameter and further larger viruses of 300 nm in diameter. For physical removal of these virus groups by the membrane filtration method, microporous membranes of at most 100 nm in maximum pore diameter are necessary, and recently the need for removal of smaller viruses such as parvoviruses has increased.
On the other hand, virus removing membranes used for purification of plasma fraction preparations and bio-medicines are required to have not only the virus removing performance, but also a high permeability to physiological active substances such as albumin and globulin. Therefore, ultrafiltration membranes having a pore diameter of about several nm or reverse osmosis membranes having even smaller pore diameters are not suitable as virus removing membranes.
Furthermore, even if microporous membranes have pore diameters suitable for removal of viruses, those which have large voids inside the membranes and bear their filtration characteristics by the surface skin layer are low in certainty for removal of viruses. This is because there are always present significant defects such as pin holes and cracks in the skin layer, and the inside of the membrane hardly contributes to removal of viruses owing to the large voids present therein. Therefore, in order to surely remove viruses, microporous membranes having uniform structure containing substantially no large voids inside the membranes are desired. The skin layer here means a very thin layer which is present on one or both sides of the membrane and has a denser structure as compared with the other inner portions of the membrane.
Furthermore, since preparations such as plasma fraction preparations and bio-medicines are generally highly viscous liquids, application of high filtration pressure in filtration to increase filtration rate is preferred in terms of high industrial productivity. Therefore, high-strength microporous membranes are necessary which do not undergo breakage, rupture, damaging, and dimensional distortion under high filtration pressure. Especially, filtration pressure applied to microporous membranes tends to increase with decrease of the pore diameter, and very high strength is required for withstanding the high filtration pressure.
Moreover, medical separating membranes are subjected to some sterilization treatment at the final step for assuring safety as products. The sterilization treatment includes a method of using medicines, a method of irradiation with ultraviolet rays or γ rays, a method of heating with steam, and others. If medicines are used, there is some concern about the slight amount of residual medicines in the separating membranes which may adversely affect human bodies. Use of ultraviolet rays is not suitable for sterilization of opaque materials because of low transmission of ultraviolet rays. Use of γ rays may inflict irradiation damage on the separating membranes and is, hence, doubtful in reliability. The method of using steam is the safest and surest method and is suitable. Therefore, materials of microporous membranes used for medical separating membranes are required to have heat resistance since the membranes must be subjected to steam sterilization at high temperatures.
Furthermore, in many cases, protein which is a component of preparations adsorbs to the separating membranes to cause clogging of micropores of the separating membranes, resulting in troubles such as reduction of permeation amount or deterioration of the components of the preparations. Accordingly, the medical separating membranes are sometimes required to have hydrophilic properties in order to prevent adsorption of protein. Preferred materials are those to which hydrophilic properties can be imparted, depending on their applications.
Conventional microporous membranes have any of the following defects: (1) they do not have such pore diameter as capable of sufficiently removing small viruses such as parvoviruses; (2) they have large voids and hence have no secure virus removing ability; (3) they have a very dense skin layer on the surface and hence cannot sufficiently permeate effective physiologically active substances such as globulin; (4) they are so low in strength that they cannot stand high filtration pressure and that sufficient filtration rate cannot be obtained; (5) they do not have heat resistance high enough to withstand steam sterilization; and the like.
Moreover, in the applications other than medical separating membranes, high performances are required in distribution of pore diameter, sectional structure of membranes, strength, heat resistance, etc. For example, as filters for industrial processing which remove fine particles, sediments or impurities in purification of chemicals, waste water disposal, or pre-production of pure water, there are generally used filters made of polytetrafluoroethylene resin or metals. What is required for filters for industrial processing is that they have a wide spectrum of pore diameters applicable to fine particles with various sizes, comprise materials having chemical resistance, and withstand the use at high temperatures and have enough strength to withstand high filtration pressures. Moreover, since they are general-purpose filters, they must be low in cost.
However, although filters made of polytetrafluoroethylene resin have excellent heat resistance, the materials are expensive and productivity is low. Although filters made of metals also have excellent heat resistance, they are inferior in ability to remove fine particles because they are composed of mesh woven fabrics or sintered materials. Therefore, techniques that can cover a wide spectrum of pore diameters and can provide inexpensive microporous membranes are earnestly demanded.
In addition, microporous membranes are utilized as membranes for separating oil and water or for separating liquid and gas, separating membranes for purification of tap water and sewage, and separators of lithium ion batteries or supports for solid electrolytes of polymer batteries, and they are required to have high performances as to pore size distribution, sectional structure of membrane, strength and heat resistance.
JP-A-3-502180 and JP-A-5-506883 disclose porous materials made of thermoplastic resins or polyvinylidene fluoride resins and comprising a polymer strand structure formed by thermally-induced liquid-liquid phase separation. According to these patent publications, since liquid-liquid phase separation mechanism is applied, these porous materials consist only of layer (B) as mentioned in claim 1 of the present invention, in which micropores are intra-spherulitic voids and inter-spherulitic voids and only microporous membranes having large pore diameters of submicron order, namely, not less than 0.1 μm, can be obtained and microviruses cannot be removed. Furthermore, strength of microporous membranes tends to be somewhat inferior.
Various technologies using non-solvent induction type phase separation which is the so-called wet method have hitherto been disclosed, for example, in JP-A-58-91732 and JP-A-59-16503. These patent publications disclose that the membranes do not contain microvoids of more than 20 μm.
Furthermore, JP-A-7-265674 discloses a polyvinylidene fluoride membrane usable for removal of viruses from solutions. According to these non-solvent induction type phase separation methods, the spherulites which constitute layer (A) as mentioned in claim 1 of the present invention are not produced, and the resulting microporous membranes have the defect of considerably low strength.
JP-A-59-64640 discloses microporous sheet materials made of thermoplastic resins formed by thermally-induced solid-liquid phase separation. Although this patent publication also discloses technology relating to polyvinylidene fluoride resins, the layer structure of section of the microporous materials is constituted only of the layer (B) where the micropores are intra-spherulitic voids and inter-spherulitic voids as shown in Comparative Example 1 in the present specification, and hence the materials are considerably brittle.